BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a disease of increasing global prevalence and an important risk factor for the development of insulin resistance,type 2 diabetes,non-alcoholic steatohepatitis and ...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a disease of increasing global prevalence and an important risk factor for the development of insulin resistance,type 2 diabetes,non-alcoholic steatohepatitis and hepatocellular carcinoma,but the pathogenesis is not clear.The aim of this study was to explore the role of ILF3 in NAFLD.AIM To investigate the molecular processes through which ILF3 facilitates the advancement of NAFLD by inhibiting the expression of p-AMPK.This exploration seeks to provide new insights into the etiology of NAFLD and evaluate the potential of ILF3 as a diagnostic marker and potential treatment focus for future interventions.METHODS In vitro and in vivo experiments were conducted using HepG2 cells and NAFLD animal models.The effects of ILF3 knockdown on lipid synthesis and triglyceride(TG)secretion were examined by analyzing the expression levels of p-AMPK.Additionally,the roles of ILF3 and the AMPK signaling pathway were verified using techniques such as Western blotting,quantitative reverse transcription PCR,Oil Red O staining,and immunohistochemistry.RESULTS Investigations revealed an increase in ILF3 Levels within both HepG2 cells and animal models of NAFLD,concurrently with a decrease in p-AMPK expression.Knocking down ILF3 activated the AMPK pathway,reducing lipid production and TG secretion in hepatocytes,thereby mitigating the advancement of NAFLD.CONCLUSION ILF3 promotes the evolution of NAFLD by inhibiting the expression of p-AMPK.The knockdown of ILF3 activates the AMPK signaling pathway,alleviating the severity of NAFLD.These findings underscore the function of ILF3 in the pathogenesis of NAFLD and demonstrate its viability as a treatment focus and diagnostic indicator.展开更多
Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability.The telomeric repeat-containing RNA(TERRA)that is transcribed from subtelomeric regions can invade into double-stran...Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability.The telomeric repeat-containing RNA(TERRA)that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called R-loop.In tumor cells,R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres(ALT)pathway.Dysregulated R-loops can cause stalled replication forks and telomere instability.However,how R-loops are recognized and regulated,particularly at telomeres,is not well understood.We discovered that ILF3 selectively associates with telomeric R-loops and safeguards telomeres from abnormal homologous recombination.Knocking out ILF3 results in excessive R-loops at telomeres and triggers telomeric DNA damage responses.In addition,ILF3 deficiency disrupts telomere homeostasis and causes abnormalities in the ALT pathway.Using the proximity-dependent biotin identification(BioID)technology,we mapped the ILF3 interactome and discovered that ILF3 could interact with several DNA/RNA helicases,including DHX9.Importantly,ILF3 may aid in the resolution of telomeric R-loops through its interaction with DHX9.Our findings suggest that ILF3 may function as a reader of telomeric R-loops,helping to prevent abnormal homologous recombination and maintain telomere homeostasis.展开更多
基金Supported by the Wuhan Science and Technology Bureau Project,No.2022020801020552(to Zhan T)Wuhan Health and Family Planning Commission Medical Research Project,No.WX20M01(to Tian X).
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a disease of increasing global prevalence and an important risk factor for the development of insulin resistance,type 2 diabetes,non-alcoholic steatohepatitis and hepatocellular carcinoma,but the pathogenesis is not clear.The aim of this study was to explore the role of ILF3 in NAFLD.AIM To investigate the molecular processes through which ILF3 facilitates the advancement of NAFLD by inhibiting the expression of p-AMPK.This exploration seeks to provide new insights into the etiology of NAFLD and evaluate the potential of ILF3 as a diagnostic marker and potential treatment focus for future interventions.METHODS In vitro and in vivo experiments were conducted using HepG2 cells and NAFLD animal models.The effects of ILF3 knockdown on lipid synthesis and triglyceride(TG)secretion were examined by analyzing the expression levels of p-AMPK.Additionally,the roles of ILF3 and the AMPK signaling pathway were verified using techniques such as Western blotting,quantitative reverse transcription PCR,Oil Red O staining,and immunohistochemistry.RESULTS Investigations revealed an increase in ILF3 Levels within both HepG2 cells and animal models of NAFLD,concurrently with a decrease in p-AMPK expression.Knocking down ILF3 activated the AMPK pathway,reducing lipid production and TG secretion in hepatocytes,thereby mitigating the advancement of NAFLD.CONCLUSION ILF3 promotes the evolution of NAFLD by inhibiting the expression of p-AMPK.The knockdown of ILF3 activates the AMPK signaling pathway,alleviating the severity of NAFLD.These findings underscore the function of ILF3 in the pathogenesis of NAFLD and demonstrate its viability as a treatment focus and diagnostic indicator.
基金National Natural Science Foundation(Grant Nos.82271598,81871109,82071587,31930058,32330023 and 32170757)National Key Research and Development Program of China(2018YFA0107003)Guang Dong Basic and Applied Basic Research Foundation(2020A1515010462).
文摘Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability.The telomeric repeat-containing RNA(TERRA)that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called R-loop.In tumor cells,R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres(ALT)pathway.Dysregulated R-loops can cause stalled replication forks and telomere instability.However,how R-loops are recognized and regulated,particularly at telomeres,is not well understood.We discovered that ILF3 selectively associates with telomeric R-loops and safeguards telomeres from abnormal homologous recombination.Knocking out ILF3 results in excessive R-loops at telomeres and triggers telomeric DNA damage responses.In addition,ILF3 deficiency disrupts telomere homeostasis and causes abnormalities in the ALT pathway.Using the proximity-dependent biotin identification(BioID)technology,we mapped the ILF3 interactome and discovered that ILF3 could interact with several DNA/RNA helicases,including DHX9.Importantly,ILF3 may aid in the resolution of telomeric R-loops through its interaction with DHX9.Our findings suggest that ILF3 may function as a reader of telomeric R-loops,helping to prevent abnormal homologous recombination and maintain telomere homeostasis.
